http://www.nlm.nih.gov/medlineplus/ency/presentations/100168_3.htm

Venous thrombosis can cause swelling and pain of the leg in which it forms. Large clots can also break free and travel to the heart and lungs, where they can cause cardiac arrest and sometimes death. This is called pulmonary embolism.

http://www.vdf.org/interactive/AskDocTranscript0510.php

Irene: How accurate is the D-Dimer blood test for showing if a blood clot is in the calf?

Speaker- Dr. Gornik: Hi Irene. In re: D-Dimer, I don't have numbers for sens/spec for calf vs. proximal leg DVT off top of my head, however, I would say that for d-dimer testing, it's a great test to "rule out" a DVT with a high negative predictive value. The negative predictive value for a low d-dimer is > 90-95%. I suspect it performs a little bit less at ruling out small clots in the calf.In regards to d-dimer, it’s important to note that while a normal d-dimer can be helpful to "rule out" DVT, a high d-dimer can be caused by lots of things, not just DVT, and you still need an ultrasound to diagnose DVT.

http://www.vdf.org/diseaseinfo/pe/diagnosis.php

How is Pulmonary Embolis Diagnosed?The definitive diagnosis of PE must be made in a hospital or clinic with radiology facilities. A chest CT scan (“CAT scan”) or a nuclear medicine scan are the most common tests to establish the diagnosis of PE. The most crucial point is for patients and their health care providers to consider the possibility of PE. Prior to chest CT scanning or a nuclear medicine scan, doctors may determine the likelihood of PE by doing screening tests such as a chest X-ray, electrocardiogram, and blood test called a “D-dimer.”  Low D-dimer levels virtually exclude PE. http://www.vdf.org/diseaseinfo/pe/diagnosis.phpHow is Pulmonary Embolis Diagnosed?The definitive diagnosis of PE must be made in a hospital or clinic with radiology facilities. A chest CT scan (“CAT scan”) or a nuclear medicine scan are the most common tests to establish the diagnosis of PE. The most crucial point is for patients and their health care providers to consider the possibility of PE. Prior to chest CT scanning or a nuclear medicine scan, doctors may determine the likelihood of PE by doing screening tests such as a chest X-ray, electrocardiogram, and blood test called a “D-dimer.”  Low D-dimer levels virtually exclude PE. http://www.aacc.org/publications/cln/2009/april/Pages/series0409.aspx

April 2009 Clinical Laboratory News: D-Dimer

 

April 2009: Volume 35, Number 4

D-DimerA Non-invasive Triage Test for Patients with Suspected DVT By Shiu-Ki Rocky Hui, MD, and Alan E. Mast, MD, PhD 

Deep venous thrombosis (DVT) affects more than 250,000 people in the U.S. each year. In particular, pregnant women, the elderly, and patients with malignancy are at increased risk for developing DVT; however, the condition can occur at any age. It mainly affects the large veins in the lower leg and thigh. Undiagnosed and untreated DVT is particularly dangerous because of the risk of a pulmonary embolism. Not only can a clot block blood flow in the lower extremities, but it also can break off and move through the bloodstream, lodging in the lungs, leading to severe damage and even death. Patients can also develop postphlebitic syndrome if DVT causes structural damage to the venous valves.

While timely antithrombotic therapy significantly reduces both DVT morbidity and mortality, the treatment poses the risk of bleeding, making accurate diagnosis of patients with suspected DVT critical. However, diagnosis presents a number of challenges for physicians. The clinical symptoms of lower extremity DVT, such as leg swelling and pain, are non-specific and can be confused with other conditions, including cellulitis, Baker’s cyst, musculoskeletal injury, and lymphedema.

Currently, the gold standard test for diagnosis of DVT is contrast venography, a procedure that requires injection of a contrast material. Because it is time-consuming, expensive, and, perhaps most importantly, risky for patients with poor renal function, contrast venography is only used rarely as a screening test, especially in ambulatory care or emergency settings. Compression ultrasound has become the diagnostic method of choice for suspected DVT, despite the fact that this procedure is also time-consuming and expensive. True DVT is identified in only 10% to 25% of patients receiving a diagnostic evaluation for DVT, although many patients present with the typical symptoms.

A rapid, low-cost, and simple peripheral blood test with good accuracy and reproducibility would provide a valuable tool for physicians to rule out the presence of DVT, as well as reduce the need for more time-consuming and expensive testing. Testing for plasma D-dimer in the ambulatory care or emergency setting has emerged as an excellent non-invasive triage test for patients with suspected DVT. The test has a high negative-predictive value (NPV) for DVT when used properly.

Here we describe how laboratorians can help ensure accurate diagnosis of this common and potentially life-threatening condition.

Biochemistry of D-dimerFibrinogen consists of a six-peptide molecule with two terminal D domains and a central E domain (Figure 1). Thrombin cleaves fibrinopeptides A and B from E domain region, producing the soluble fibrin monomer. These monomers are then assembled with end-to-end and side-to-side association to form non-covalent fibrin polymers. Factor XIIIa crosslinks these fibrin polymers by catalyzing isopeptide bond formation between the γ-chains in the D domain of the adjacent monomers, which result in an insoluble cross-linked fibrin clot. When plasmin, the end product of the fibrinolytic system, is formed, it degrades insoluble, cross-linked fibrin via cleavage of the α-, β-, and γ-chains and results in the liberation of a variety of fibrin degradation products (FDPs) with a large range of molecular weights. Among these FDPs is the D-dimer, a fragment with a molecular weight of ~180kDa (Figure 1).

Given this biochemical scheme, the presence of D-dimer in blood corresponds to the in vivo formation and

degradation of a fibrin clot. Since 2% to 3% of plasma fibrinogen is physiologically converted to cross-linked fibrin and then degraded, small amounts of D-dimer are normally present in the plasma of healthy individuals. But when the coagulation and fibrinolytic cascades are activated in vivo, as is the case with DVT, the plasma concentration of D-dimer increases dramatically. The converse is also true: plasma D-dimer concentration decreases in response to anticoagulant therapy and the resolution of symptoms. The protein has a plasma half-life of approximately 8 hours and clearance occurs mainly via the kidneys and reticulo-endothelial system.

Measurement of D-dimerD-dimer contains a neo-epitope that is formed following the cross-linking of adjacent D domains by factor XIIIa. It is this epitope that is recognized by specific antisera used in clinical assays. Koopman and coworkers introduced one of the first clinical assays for D-dimer in 1987, a solid-phase EIA containing a mouse monoclonal antibody that specifically recognized cross-linked fibrin degradation products and not degradation products of fibrinogen or uncross-linked fibrin.

Currently, more than 30 different D-dimer assays are commercially available. While these assays represent a wide range of techniques (Table 1), the fundamental principle of the D-dimer assay has remained largely unchanged: recognition of the unique neo-epitope in D-dimer by specific antisera.

The classic microplate ELISA was considered the gold standard for measuring D-dimer. However, due to the time-consuming and labor-intensive nature of the ELISA technique, it has limited utility in the rapid diagnosis of DVT, especially in outpatient and emergency room settings. Modified ELISA methods have now replaced the microplate ELISA method.

These newer assays use more robust final detection methods such as fluorescence, chemiluminescence, or time-resolved fluorescence, allowing the assays to be automated and reducing the turn-around time to approximately 30 minutes. Quantitative latex agglutination with photometric or turbidimetric detection provides a fully automated and rapid method for D-dimer assays that can be performed on routine coagulation or clinical chemistry analyzers and eliminates the need for dedicated instruments.

Point-of-care (POC) methods, such as the semi-quantitative latex agglutination-based system, provide very rapid bedside testing that does not require complicated instrumentation. However, since most of these POC systems require subjective visual reading of agglutination, inter-observer variability makes them less sensitive than automated methods and greatly limits their clinical utility. Recently, manufacturers have developed a POC D-dimer assay that eliminates visual reading of agglutination and provides fully automated bedside testing. These POC devices can quantitatively measure D-dimer in plasma and whole blood and have minimal turn-around times. Such POC devices may be valuable for rapid rule-out of DVT in the outpatient clinic without the need of more costly and time-consuming imaging studies.

Standardization of D-dimer AssaysLabs typically determine the diagnostic cutoff values for D-dimer from assay-specific reference curves established using the manufacturer’s calibrators. The numeric results of D-dimer assays are reported either as D-dimer concentration (assays that use purified fibrin fragment D-dimer as the calibrator) or fibrinogen-equivalent units (FEUs)—assays that use purified fibrinogen for preparation of a fibrin clot and degradation by plasmin as the calibrator. Laboratorians can transform D-dimer concentration to FEU based on the concept that one unit of FEU is approximately twice the mass of one unit of D-dimer (2FEU=1 D-dimer). Therefore, multiplying the D-dimer concentration by 2 converts the mass to the approximate FEU concentration.

Walker and Nesheim have demonstrated that there is a wide spectrum of D-dimer-containing FDPs released from a fibrin clot via the fibrinolytic action of plasmin. All of these D-dimer-containing FDPs react with the specific D-dimer antibodies. Therefore, the reported D-dimer concentration or FEU actually represents the measurement of a heterogeneous mixture of D-dimer-containing FDPs, while the “true” D-dimer concentration is the amount of cross-linked D-domains present in a sample, irrespective of the size of the FDPs. Since each assay has its own calibrator that is made from either purified D-dimer or plasmin proteolysis products of fibrin clots, these calibrators do not

necessarily mirror the heterogeneous nature of D-dimer-containing FDPs in a clinical sample. As a result, the value of D-dimer measured in a sample can vary greatly depending on which assay was used and how it was calibrated. Currently, there is no established reference method, primary standard, or a standard universal calibrator for the D-dimer assay.

This lack of standardization is well illustrated in the 2007 College of American Pathologists (CAP) survey results. The 196 labs participating in the survey used 12 different methods to measure D-dimer. The reported mean D-dimer value for these assays varied from 269.69 ng/mL to 2,449.92 ng/mL. On the other hand, the intra-assay variability between labs was much lower, with the majority of assays having CV of <10%, indicating that intra-assay precision is generally good. In addition, manufacturers typically recommended that each lab establish its own reference range. Without a universal standardization of D-dimer, it can be difficult for individual labs to determine a proper cut-off value to rule out DVT. There have been multiple attempts to standardize the various quantitative D-dimer methods; however, none is currently in place. Because of the inherent differences in the various D-dimer assays, laboratorians need to pay close attention to the specific D-dimer methods used in published clinical studies. The same cutoff values may not apply unless the lab uses the same manufacturer’s assay.

D-Dimer for Diagnosis of DVTFalse-negative results from a D-dimer assay can lead to serious and potentially fatal clinical consequences. When a lab picks a D-dimer assay for diagnosing DVT, it is important to select an assay with high sensitivity and a low CV at the cutoff to minimize false-negative results. The specificity of the assay should also not be overlooked, because a high rate of false-positive results can lead to unnecessary imaging studies and anticoagulation treatments.

While there are some trade-offs between sensitivity and specificity among the various methods, all the commercially available assays have comparable clinical utility. In general, in the setting where the D-dimer will serve as a first-step diagnostic tool to rule out DVT, labs should select an assay with high sensitivity. However, if the D-dimer test is used in conjunction with other tests, a less sensitive and more specific assay should be used to avoid unnecessary additional testing.

Multiple clinical studies have produced efficient algorithms that integrate D-dimer testing into the diagnosis of DVT in ambulatory care and emergency settings (Figure 2). Wells and co-workers demonstrated that the use of a manual, whole-blood agglutination D-dimer test in combination with a scoring system for clinical pretest probability, known as the Wells score, resulted in a significant reduction in the number of patients having compression ultrasound testing performed. In another study, Bates and co-workers demonstrated that a negative immuno-turbidimetric D-dimer test, along with a low-to-moderate pretest probability effectively rules out the presence of DVT.

Figure 2 Sample Algorithm for Incorporating D-dimer Testing in the

Diagnosis of DVT in Ambulatory Care Setting

 

Adapted from Hargett CW, Tapson VF. Clinical probability and D-dimer testing: How should we use them in clinical practice? Semin Respir Crit Care Med 2008;29:15–24.

While the use of D-dimer testing to rule out DVT in the ambulatory care setting is well established, its use in the elderly, pregnant women, and patients with recurrent DVT is less clear. Researchers hypothesized that these patients may have increased D-dimer in the absence of DVT compared to general patients in the outpatient setting. However, several recent studies aimed at resolving these issues have not proven this to be the case.

Carrier and co-workers found that among patients ages 60 to 80, a low-to-unlikely Wells score in combination with a negative D-dimer test (manual, whole-blood agglutination, or immuno-turbidimetric) result had a 99% NPV. However, in patients greater than 80 years, the NPV of a low-to-unlikely Wells score in combination with a negative D-dimer result has an NPV of only 21 to 31%. Chan and co-workers performed a similar study of pregnant patients and found that a low pretest probability and a negative D-dimer (manual, whole-blood agglutination) had an NPV of 100%. Rathbun and co-workers also studied the effectiveness of D-dimer (immuno-turbidimetric assay) in excluding recurrent DVT. They demonstrated that of the patients with a negative D-dimer test at presentation only 0.75% had a confirmed diagnosis of symptomatic venous thromboembolism at 3 months follow-up. Therefore, it appears that measurement of D-dimer is useful for ruling out DVT in these more complicated patient populations.

Making the Right Choice Despite the lack of assay standardization, D-dimer testing is an effective, inexpensive, and rapid diagnostic tool for ruling out the presence of DVT in ambulatory care and emergency patients. In combination with a low-to-moderate pretest probability, a negative D-dimer test can efficiently eliminate the need for more expensive and time-consuming imaging studies. In selecting a D-dimer assay, it is important to understand what clinical role D-dimer testing will play. If the intention is to rule out the diagnosis of DVT without the need for further studies, then labs should select an assay with high sensitivity and NPV to minimize false-negative results. But no matter which assay a lab chooses to use, laboratorians need to emphasize to their physician customers that a proper clinical evaluation and evidence-based pretest probability is vital for the proper interpretation of D-dimer assay results.

http://labtestsonline.org/understanding/analytes/d-dimer/tab/test

D-dimer

Also known as: Fragment D-dimer; Fibrin degradation fragmentFormal name: D-dimerRelated tests: Fibrin Degradation Products (FDP); Fibrin Split Products (FSP); Prothrombin Time (PT); Partial Thromboplastin Time (PTT); Fibrinogen; Platelet Count

At a Glance Test Sample The Test Common Questions Ask Us Related Pages

The Test1. How is it used? 2. When is it ordered? 3. What does the test result mean? 4. Is there anything else I should know?

How is it used?D-dimer tests are ordered, along with other laboratory tests and imaging scans, to help rule out the presence of a thrombus. Some of the conditions that the d-dimer test is used to help rule out include:

Deep vein thrombosis (DVT) Pulmonary embolism (PE) Strokes

This test may be used to determine if further testing is necessary to help diagnose diseases and conditions that cause hypercoagulability, a tendency to clot inappropriately.

A D-dimer level may be used to help diagnose disseminated intravascular coagulation (DIC) and to monitor the effectiveness of DIC treatment.

When is it ordered?D-dimer may be ordered when someone has symptoms of DVT, such as:

Leg pain or tenderness, usually in one leg Leg swelling, edema Discoloration of the leg

It may be ordered when someone has symptoms of pulmonary embolism such as: Sudden shortness of breath, labored breathing Coughing, hemoptysis (blood present in sputum) Lung-related chest pain Rapid heart rate

D-dimer is especially useful when the doctor thinks that something other than DVT or PE is causing the symptoms. It is a quick, non-invasive way for the doctor to help rule out abnormal or excess clotting.

When a person has symptoms of DIC, such as bleeding gums, nausea, vomiting, severe muscle and abdominal pain, seizures, and decreased urine output, a D-dimer test may be ordered, along with a PT, PTT, fibrinogen, and platelet

count to help diagnose the condition. D-dimer may also be ordered at intervals when a patient is undergoing treatment for DIC to help monitor its progress.

What does the test result mean?

A normal or negative D-dimer result means that it is most likely that the person tested does not have an acute condition or disease that is causing abnormal clot formation and breakdown. Most doctors agree that a negative D-dimer is most valid and useful when the test is done on people who are considered to be at low to intermediate risk for thrombosis. The test is used to help rule out clotting as the cause of symptoms.

A positive D-dimer result may indicate the presence of an abnormally high level of fibrin degradation products. It tells the doctor that there may be significant blood clot (thrombus) formation and breakdown in the body, but it does not tell the location or cause. It may be due to, for example, a venous thromboembolism (VTE) or DIC. Typically, the D-dimer level is very elevated in DIC.

However, an elevated D-dimer does not always indicate the presence of a clot because a number of other factors can cause an increased level. Elevated levels may be seen in conditions in which fibrin is formed and then broken down, such as recent surgery, trauma, infection, heart disease, and some cancers or conditions in which fibrin is not cleared normally, such as liver disease. Therefore, D-dimer is typically not used to rule out VTE in hospitalized patients (inpatient setting).

Pregnancy is also a condition in which fibrin is formed and broken down and may result in an elevated D-dimer level. However, if DIC is suspected in a woman who is pregnant or is in the immediate postpartum period, then the D-dimer test may be used, along with a PT, PTT, fibrinogen, and platelet count to help diagnose her condition. If the woman has DIC, her D-dimer level will be very elevated.

D-dimer is recommended as an adjunct test. It should not be the only test used to diagnose a disease or condition. Both increased and normal D-dimer levels may require followup and can lead to further testing.

When used to monitor DIC treatment, decreasing levels indicate that treatment is effective while increasing levels may indicate that treatment is not working.

Is there anything else I should know?D-dimer concentrations may rise in the elderly, and false positives may be seen with high levels of rheumatoid factor, a protein seen in patients with rheumatoid arthritis. Substances such as high triglycerides, lipemia, and bilirubin can also cause false positives as can hemolysis caused by improper sample collection and handling.

There are several different methods of testing for D-dimer. Most of the D-dimer tests that yield quantitative results are done in a hospital lab, while those that yield qualitative or semi-quantitative results are performed at the patient's bedside (point of care).

http://labtestsonline.org/understanding/analytes/d-dimer/t ©2008 American Association for Clinical Chemistry 1850 K Street, NW Suite 625Washington, DC 20006Phone: (800) 892-1400 | Fax: (202) 887-5093

ab/glance

D-dimer

Also known as: Fragment D-dimer; Fibrin degradation fragment

Formal name: D-dimer

Related tests: Fibrin Degradation Products (FDP); Fibrin Split Products (FSP); Prothrombin Time (PT); Partial Thromboplastin Time (PTT); Fibrinogen; Platelet Count

At a GlanceWhy Get Tested?To help rule out clotting (thrombotic) episodes and to help diagnose conditions related to thrombosis

When to Get Tested?When you have symptoms of a thrombotic episode or a condition that causes acute and/or chronic inappropriate blood clot formation such as deep vein thrombosis (DVT), pulmonary embolism (PE), or disseminated intravascular coagulation (DIC) and to monitor the progress and treatment of DIC and other thrombotic conditions

Sample Required?A blood sample drawn from a vein in your arm

Test Preparation Needed?None

The Test SampleWhat is being tested?D-dimer is one of the protein fragments that are produced when a blood clot dissolves in the body. When a blood vessel or tissue is injured and begins to bleed, a process called hemostasis is initiated by the body to create a blood clot to limit and eventually stop the bleeding. During this process, threads of a protein called fibrin are produced. These threads crosslink together to form a fibrin net, which, together with platelets, helps hold the forming blood clot in place at the site of the injury until it heals.

Once the area has had time to heal and the clot is no longer needed, the body uses an enzyme called plasmin to break the clot (thrombus) into small pieces so that it can be removed. The fragments of the disintegrating fibrin in the clot are called fibrin degradation products (FDP). One of the fibrin degradation products produced is D-dimer, which consists of variously sized pieces of crosslinked fibrin.

D-dimer is normally undetectable in the blood and is produced only after a clot has formed and is in the process of being broken down. When there is significant formation and breakdown of blood clots in the body, the D-dimer blood level can rise. The D-dimer test measures the level in the blood.

For a person who is at low or intermediate risk for thrombosis and/or thrombotic embolism, the strength of the D-dimer test is in its negative predictive value in a hospital emergency room setting. That means that a negative D-dimer test indicates that it is highly unlikely that a thrombus is present. However, a positive d-dimer test cannot predict whether or not a clot is present. It indicates that further testing is required.

There are several factors and conditions that are associated with inappropriate blood clot formation. One of the most common of these conditions is deep vein thrombosis (DVT), which involves clot formation in the deep veins of the body, most frequently in the legs. These clots may grow very large and block blood flow in the legs, causing swelling, pain, and tissue damage. It is possible for a piece of the clot to break off and travel to other parts of the body. This "embolus" can lodge in the lungs, causing a pulmonary embolus or embolism (PE).

While clots most commonly form in the veins of the legs, they may also form in other areas as well; for example, clots in coronary arteries are the cause of myocardial infarction (heart attacks). Clots may also form on the lining of the heart or its valves, particularly when the heart is beating irregularly (atrial fibrillation) or when the valves are damaged. Clots also may form in large arteries as a result of narrowing and damage from atherosclerosis. Pieces of such clots may also break off and cause an embolus that blocks an artery in another organ, such as the brain (causing a stroke) or the kidneys. Measurements of D-dimer can be used to help detect clots in any of these sites.

Measurements of D-dimer may also be ordered, along with other tests, to help diagnose disseminated intravascular coagulation (DIC). The D-dimer level will typically be very elevated in DIC. DIC is a complex, acute, sometimes life-threatening condition that can arise from a variety of situations including some surgical procedures, sepsis, poisonous snake bites, liver disease, and postpartum (after the delivery of a baby). With DIC, clotting factors are activated and then used up throughout the body. This creates numerous tiny blood clots and at the same time leaves the patient vulnerable to excessive bleeding. Steps are taken to support the affected person while the underlying condition resolves.

How is the sample collected for testing?A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?No test preparation is needed.

The Test1. How is it used? 2. When is it ordered? 3. What does the test result mean? 4. Is there anything else I should know?

How is it used?D-dimer tests are ordered, along with other laboratory tests and imaging scans, to help rule out the presence of a thrombus. Some of the conditions that the d-dimer test is used to help rule out include:

Deep vein thrombosis (DVT) Pulmonary embolism (PE)

Strokes

This test may be used to determine if further testing is necessary to help diagnose diseases and conditions that cause hypercoagulability, a tendency to clot inappropriately.

A D-dimer level may be used to help diagnose disseminated intravascular coagulation (DIC) and to monitor the effectiveness of DIC treatment.

When is it ordered?D-dimer may be ordered when someone has symptoms of DVT, such as:

Leg pain or tenderness, usually in one leg Leg swelling, edema Discoloration of the leg

It may be ordered when someone has symptoms of pulmonary embolism such as: Sudden shortness of breath, labored breathing Coughing, hemoptysis (blood present in sputum) Lung-related chest pain Rapid heart rate

D-dimer is especially useful when the doctor thinks that something other than DVT or PE is causing the symptoms. It is a quick, non-invasive way for the doctor to help rule out abnormal or excess clotting.

When a person has symptoms of DIC, such as bleeding gums, nausea, vomiting, severe muscle and abdominal pain, seizures, and decreased urine output, a D-dimer test may be ordered, along with a PT, PTT, fibrinogen, and platelet count to help diagnose the condition. D-dimer may also be ordered at intervals when a patient is undergoing treatment for DIC to help monitor its progress.

What does the test result mean?

A normal or negative D-dimer result means that it is most likely that the person tested does not have an acute condition or disease that is causing abnormal clot formation and breakdown. Most doctors agree that a negative D-dimer is most valid and useful when the test is done on people who are considered to be at low to intermediate risk for thrombosis. The test is used to help rule out clotting as the cause of symptoms.

A positive D-dimer result may indicate the presence of an abnormally high level of fibrin degradation products. It tells the doctor that there may be significant blood clot (thrombus) formation and breakdown in the body, but it does not tell the location or cause. It may be due to, for example, a venous thromboembolism (VTE) or DIC. Typically, the D-dimer level is very elevated in DIC.

However, an elevated D-dimer does not always indicate the presence of a clot because a number of other factors can cause an increased level. Elevated levels may be seen in conditions in which fibrin is formed and then broken down, such as recent surgery, trauma, infection, heart disease, and some cancers or conditions in which fibrin is not cleared normally, such as liver disease. Therefore, D-dimer is typically not used to rule out VTE in hospitalized patients (inpatient setting).

Pregnancy is also a condition in which fibrin is formed and broken down and may result in an elevated D-dimer level. However, if DIC is suspected in a woman who is pregnant or is in the immediate postpartum period, then the D-dimer test may be used, along with a PT, PTT, fibrinogen, and platelet count to help diagnose her condition. If the woman has DIC, her D-dimer level will be very elevated.

D-dimer is recommended as an adjunct test. It should not be the only test used to diagnose a disease or condition. Both increased and normal D-dimer levels may require followup and can lead to further testing.

When used to monitor DIC treatment, decreasing levels indicate that treatment is effective while increasing levels may indicate that treatment is not working.

Is there anything else I should know?D-dimer concentrations may rise in the elderly, and false positives may be seen with high levels of rheumatoid factor, a protein seen in patients with rheumatoid arthritis. Substances such as high triglycerides, lipemia, and bilirubin can also cause false positives as can hemolysis caused by improper sample collection and handling.

There are several different methods of testing for D-dimer. Most of the D-dimer tests that yield quantitative results are done in a hospital lab, while those that yield qualitative or semi-quantitative results are performed at the patient's bedside (point of care).

Common Questions1. What are some common risk factors for inappropriate blood clotting? 2. What other procedures may my doctor order if my D-dimer is positive?

1.  What are some common risk factors for inappropriate blood clotting? Some risk factors include:

Major surgery or trauma Hospitalization or living in a nursing home Prolonged immobility—this can include long trips by plane, car, etc. or prolonged bed rest Use of birth control or hormone replacement therapy Broken bone, cast Pregnancy or recent childbirth Antiphospholipid syndrome Certain cancers Inherited clotting disorder such as factor V Leiden mutation

2.  What other procedures may my doctor order if my D-dimer is positive? In an emergency room setting, if you are found to be at low-to-intermediate risk for thrombosis and/or venous thromboembolism and when you have a positive D-dimer test, your doctor will likely order a non-invasive scanning procedure, such as a venous ultrasound or CT angiography. Additional procedures may include ventilation/perfusion scan or pulmonary angiography. For more on these, see Radiologyinfo.org: Heart and Vascular.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC307711/

BMJ. 2009; 339: b2990.

Published online 2009 August 14. doi: 10.1136/bmj.b2990

PMCID: PMC2727580

Copyright notice

Excluding venous thromboembolism using point of care D-dimer tests in outpatients: a diagnostic meta-analysis

G J Geersing, general practitioner , 1 K J M Janssen, clinical epidemiologist,1 R Oudega, general practitioner,1 L Bax, clinical epidemiologist ,1,2 A W Hoes, professor of clinical epidemiology and primary care,1 J B Reitsma, clinical epidemiologist,3 and K G M Moons, professor of clinical epidemiology 1

1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands

.

Conclusions

Both qualitative and quantitative point of care D-dimer tests can safely exclude venous thromboembolism in low risk outpatients. Quantitative tests seem to perform better than qualitative tests, although the quantity of available data is still limited. Also, there are only few studies of these tests in patients suspected of PE. In outpatients suspected of DVT, however, point of care D-dimer tests can contribute important information and guide patient management.

What is already known on this topic

Several meta-analyses have shown that laboratory based D-dimer testing—such as enzyme linked immunosorbent assay—can be used to exclude venous thromboembolism

Excluding venous thromboembolism commonly requires referring a patient to a central laboratory facility Point of care D-dimer tests are available that could enable exclusion of venous thromboembolism in a near patient

situation; however, their diagnostic accuracy is largely unknown

What this paper adds

Point of care D-dimer tests can safely exclude venous thromboembolism in low risk outpatients Such tests can, therefore, contribute important information at the point of care and guide patient

managemenhttp://www.nursingcenter.com/library/JournalArticle.asp?Article_ID=733520

D-dimer: Past, present, and future Melissa Sumney, RN, ACNP, BSN Kimberly Whiteman, RN, MSN

Nursing2007Fall 2007 Volume 37 Number 8 - Supplement: ED Insider Pages 14 - 16

PDF Version Available!

The D-dimer level is a measure of clot formation and lysis that results from the degradation of cross-linked fibrin. Widely used as an indicator for the presence of disseminated intravascular coagulation, it's more sensitive than usual measures, such as activated partial thromboplastin time and prothrombin time (PT).1 D-dimer also has been established as a rule-out test for venous thromboembolism (VTE). In the outpatient setting, a negative D-dimer, accompanied by a low clinical probability rating (using a tool such as the Wells criteria), indicates that the overall clinical risk of the patient having a VTE is extremely low.2

Historical use

The usefulness of D-dimer testing as a diagnostic tool lies in its negative predictive value, and research has established its high sensitivity, but low specificity.3 Testing products can correctly identify D-dimer elevation, but they don't identify why D-dimer is elevated. Two classes of D-dimer testing methods reporting high negative predictive values are enzyme-linked immunosorbent assay (ELISA) D-dimer and microlatex agglutination.4 The British Thoracic Society guidelines incorporate "the most investigated assays-a whole-blood red cell agglutination assay (SimpliRED; Agen Biomedical, Brisbane, Australia) and a rapid ELISA (VIDAS; BioMerieux, L'Etoile, France)."5

In summary, a negative D-dimer correlated with a low clinical predictive value suggests that VTE isn't present.2 A negative D-dimer in conjunction with a low clinical probability offers clinicians a convenient and cost-effective diagnostic alternative to more expensive or invasive tests, such as a pulmonary angiogram (for outpatients).

Conversely, the positive predictive value of D-dimer for VTE is quite poor. Many clinical conditions can cause elevated D-dimer levels, so a positive value doesn't identify the specific cause of the elevation. The clinician can't diagnose VTE on positive D-dimer alone. (See What's normal?)

Healthy patients

In healthy patients, procoagulant and anticoagulant factors in the clotting cascade are in fine balance. Any change in the balance could place a patient at risk for VTE or bleeding. A recent study found that at certain levels, procoagulant and anticoagulant factors are grouped together in the coagulation cascade.6 Investigators believe the discovery of hereditarily high levels of certain coagulation factors is associated with increased risk of VTE, and regulatory genes may be located outside clotting factor genes that control protein levels affecting the coagulation cascade. At certain levels, researchers theorize that these regulatory proteins cause grouping together, or clustering, of procoagulant and anticoagulant factors.6 Procoagulant vitamin K-dependent factors, factor XI, and factor XII were found to cluster together. Factor V and factor VIII were found to cluster with fibrinogen and D-dimer; factor XIII remained independent. The anticoagulant factors protein C, protein S, and antithrombin also clustered together.6

Activation of the clotting cascade by a number of clinical conditions, such as endothelial injury, cancer, pregnancy, surgery, sepsis, acute respiratory distress syndrome (ARDS), and trauma, will affect D-dimer results.

Hospitalized patients

If D-dimer can be used as a rule-out tool for VTE in outpatients, why isn't it used more often in the inpatient setting? Some studies have examined the use of D-dimer in the inpatient population, and the consensus is that D-dimer isn't a reliable rule-out tool for VTE in this population.

One study cautioned against the use of D-dimer testing on inpatients due to the high rate of false-positive results in patients with active disease processes such as pneumonia, heart failure, and malignancy.7 Researchers further described the possibility of a false-negative result in patients receiving anticoagulation prophylaxis or therapy and in those patients for whom duration of symptoms is unknown or subacute. Their research showed D-dimer levels had little reliability as a rule-out tool in determining which patients did or didn't have VTE if patients met the following criteria:

* they'd been hospitalized for more than 3 days

* they were over age 60

* they had had high C-reactive protein levels.7

Researchers did document a relationship between D-dimer and C-reactive protein, supporting a connection between inflammation and thrombosis.7 For every quartile in which C-reactive protein rises, there's a correlational rise in D-dimer. The higher the two rise, the less reliable D-dimer's negative predictive value becomes. This correlation implies that as inflammation progresses, the likelihood of thromboembolism increases.7

D-dimer in the ICU

Proinflammatory states in critically ill hospitalized patients lead to elevated D-dimer levels via cytokine activation of the coagulation cascade and corresponding inhibition of fibrinolysis.8 Although D-dimer hasn't been shown to be an effective resource to rule out VTE in hospitalized patients, given the correlation of D-dimer to protein C and the inflammatory response, researchers are examining whether D-dimer could be used as a prognostic tool for mortality in the emergency department or intensive care unit (ICU), where activation of the inflammatory response is prominent.

Virchow's triad and the subsequent activation of the clotting cascade through physiologic activity, such as the inflammatory process, can result in microthrombi, which has been implicated in sepsis, ARDS, and multisystem organ failure.9 Sepsis mortality is directly related to the number and severity of organs affected. Many studies show coagulation abnormalities emerging before symptom onset in sepsis or shock and baseline elevation of D-dimer levels soon after the onset of the first organ system to be affected.10 One study defined baseline D-dimer as the D-dimer level the day of admission to the ICU, and the first day of severe sepsis as, "the first calendar day after the onset of the first sepsis-induced organ dysfunction."10 Researchers also correlated the degree of abnormal baseline D-dimer to 28-day mortality. Changes in PT and D-dimer were related to 28-day mortality.10

Researchers who evaluated a rapid assay D-dimer test sought to draw a parallel between D-dimer levels and poor outcomes in the critically ill by comparing Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score (SAPS) scores.9 Their findings show an association between D-dimer levels 24 hours after admission to an ICU and the 48-hour APACHE II and SAPS scores. Significant correlation was discovered between the 48-hour D-dimer level and the 48-hour APACHE II, SAPS, and the organ system failure index.9 This relationship demonstrates that the value of using D-dimer to predict clinical severity is seen 48 hours after admission to the ICU. Surprisingly, neither the 24-hour nor the 48-hour D-dimer level predicted in-hospital mortality, whereas APACHE II, SAPS, and the organ system failure index did predict mortality. However, the D-dimer level was capable of predicting the magnitude of organ failure.9 Therefore, the investigators suggest that D-dimer be used to predict general clinical severity of the critically ill patient. A particularly interesting point of the study is that the investigators included surgical patients, in whom D-dimer is expected to be elevated postoperatively.

Treating VTE involves preventing clot extension, embolization, and recurrence.8 The aim of treatment for microembolism is to limit the degree of the inflammatory response, resolve or prevent further embolization, and prevent or repair as much end organ damage as possible. The PROWESS study, which documents the efficacy of using recombinant human activated protein C to treat severe sepsis, also documents lower D-dimer levels achieved by means of treatment with activated protein C, which correlated to improved survival.8

Future trends

The use of D-dimer level as a predictor of severity of coagulopathy, inflammatory response, and mortality in the critically ill patient is becoming more widespread. Investigators are examining D-dimer as it relates to other disease states and processes. Documentation proves that D-dimer levels decline with anticoagulation, and researchers are looking toward predicting survival in patients with chronic atrial fibrillation. High mean baseline D-dimer levels are related to patients with atrial fibrillation who are receiving oral anticoagulation therapy and who had suffered cardiovascular events, including myocardial infarction, peripheral occlusion, stroke, and death.11 The study also showed that low D-dimer levels and oral anticoagulation therapy were independently correlated to survival, suggesting that a single D-dimer can predict survival over 2 years.11

Studies also have documented a correlation between D-dimer and severity of community-acquired pneumonia, as well as D-dimer's role in detecting acute aortic dissection and during cardiopulmonary bypass.12-14

The groundwork has been laid for future research into the correlation of elevated D-dimer to critical outcomes. Uncovering new ways for D-dimer to be used in hospitals has opened a new door in the advancement of caring for critically ill patients.

What's normal?

Though multiple tests are available on the market, no gold standard in which to compare results exists, so there's no "normal" value for D-dimer. With multiple products available designed to measure D-dimer levels, practitioners must be familiar with the test they're using and the respective manufacturer-recommended parameters.

Tests can be quantitative and reported in numerical units of measure, such as nanograms per milliliter, or they can be nonquantitative, which are reported as positive or negative values. Quantitative tests provide recommended cutoff

levels for positive results and units of measure such as nanograms per milliliter, milligrams per liter of fibrinogen equivalent units (FEUs), or D-dimer units. Units of measure aren't interchangeable between testing products, as each product will have its own parameters.

Nonquantitative or semi-quantitative tests rely on reader interpretation and can vary from technician to technician. For example, one study used two types of D-dimer testing products to evaluate the efficacy of D-dimer testing on inpatients versus outpatients. Although they were both measured in milligrams per liter of FEU, one product reported positive results as greater than 1.0 mg/L and the other reported positive results as greater than 4.0 mg/L.4 Though each testing kit reported positive results quantitative results in milligrams per liter, each retained its own cutoff value for a positive result. Past that positive value, the exact number wasn't reported.

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Encyclopedia of Nursing & Allied HealthFibrin Degradation Products Test

DefinitionWhen injury occurs to a blood vessel wall, thrombin (a coagulation enzyme) is formed in the first stage of a complicated series of steps called the coagulation cascade. In the second phase, fibrinogen, a coagulation protein made by the liver, is converted to fibrin, which results in the formation of a gel-like meshwork at the site. This fibrin mesh is altered by the action of factor XIIIa which cross-links fibrin polypeptides, forming a stable clot. As the site heals, the clot is broken down by the enzyme plasmin. This process, called fibrinolysis, is initiated by a protein called tissue plasminogen activator that is released from blood vessel cells adjacent to the injured site. Plasminogen activator converts plasminogen to an enzyme called plasmin. The plasmin splits polypeptides from the fibrin clot. These fragments are known as fibrin degradation products (FDP).

Fibrin degradation products are fragments (polypeptides) produced when either fibrin or fibrinogen is broken down by the enzyme plasmin. There are four principal fibrin degradation products called X, Y, D, and E that are liberated in various combinations. When a fibrin clot is broken down by plasmin, the last fragment to be degraded is one consisting of two D and one E subunits. This is split, releasing the E fragment and two D fragments that are covalently linked together. This fragment is called D-dimer, and it is produced from fibrin but not from fibrinogen degradation.

PurposeA test for FDP may be requested by a physician when excessive bleeding occurs and thrombosis or other serious disorder in the coagulation mechanism is suspected. The FDP assay measures amounts of the fibrin and fibrinogen

split products in the blood and directly indicates the level of activity of the fibrinolytic system. High levels of FDP will indicate increased fibrinolysis. Excessive fibrin degradation products are released into the plasma in three main conditions: disseminated intravascular coagulation (DIC), thromboembolytic therapy, and primary fibrinogenolysis. Fragments X, Y, E, and D are released whenever either fibrin or fibrinogen is broken down by plasmin. This degradation occurs in all three situations.

Normal blood plasma does not have significant amounts of D-dimer. It is present in the blood in detectable amounts in several conditions, most notably in disseminated intravascular coagulation (DIC), a rare disruption in normal coagulation in which rapid intramicrovascular (within the blood vessels) coagulation occurs at the same time as fibrinolysis (clot dissolution mechanism). The D-dimer test is used to diagnose DIC. It is also frequently used to help diagnose deep-vein thrombosis (clots in veins); pulmonary embolism (clots in the lungs); the thrombosis of malignancy; and sickle cell anemia (a form of anemia characterized by bleeding episodes); and to monitor the effects of thrombolytic drugs. Thrombolytic drugs that may increase D-dimer levels are barbiturates, heparin, streptokinase, and urokinase. Levels of D-dimer will be elevated in these conditions.

DescriptionWhen functioning normally, coagulation and fibrinolysis maintain hemostasis (the normal fluid state of blood in the circulatory system) by regulating clot formation and dissolution. When bleeding occurs, coagulation results in production of a clot at the site of injury, and subsequent fibrinolysis dissolves the clot as the vessel wall heals. The fibrinolytic system is highly complex. A deficiency of plasminogen will result in increased risk of thrombosis. Plasmin is inactivated by several proteases, which are enzymes that catalyze the breakdown of polypeptides. A deficiency of one of these can result in spontaneous bleeding. FDPs themselves can neutralize the activity of some coagulation factors and interferere with normal clot formation. In three conditions, disseminated intravascular coagulation, thromboembolytic therapy, and primary fibrinogenolysis the fibrinolytic activity of the plasma is increased. When this occurs, depletion of coagulation factors, including fibrinogen, results in uncontrolled bleeding. Measurement of FDP and D-dimer are used to identify these causes of hemorrhage.

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DIC results in the formation of circulating small fibrin clots formed by a condition that triggers the coagulation cascade. Coagulation factors become depleted and hemorrhage results. DIC is a rapidly progressing condition caused by an underlying disease or trauma, such as the clinical conditions shown below.

complications of pregnancy, such as toxemia, abortion, cesarean section, placenta previa, and other conditions tissue trauma, such as major surgery, severe trauma and burns, rejection of transplant, and heatstroke hemolytic processes (destruction of red blood cells), such as transfusion of mismatched blood, drowning,

complications of infection, and certain types of poisoning malignancies, such as solid tumors, leukemia, and other forms of cancer infections, such as bacterial infections, septicemia, Rocky Mountain spotted fever, some viral infections, and parasitic

infections miscellaneous clinical conditions, such as diseases of the liver and pancreas, uremia, shock, stroke, severe heart

failure, and aortic aneurysm (rupture of the aorta)

Coronary artery disease can result in the formation of a blood clot at the site of blockage in the heart vessels. One alternative form of treatment is the administration of a thrombolytic agent such as streptokinase or tissue plasminogen activator. These drugs act by stimulating fibrinolysis, and consequently they may cause both the fibrin clot and fibrinogen to break down. Fibrinogen depletion and accumulation of FDP can interfere with coagulation, causing spontaneous hemorrhage.

Primary fibrinogenolysis is a condition in which fibrinogen is broken down to fibrin in the absence of a clot. Unlike DIC, the formation of intravascular thrombi does not occur. However, if severe, hemorrhage can result because the body's supply of fibrinogen becomes depleted. Causes include shock, hypoxia, heat stroke, hemorrhage, surgery, and liver disease.

FDP tests will yield abnormal results in all three conditions described above because the fragments detected are produced when either fibrin or fibrinogen is split by plasmin. Therefore, the FDP test is not specific for thrombotic diseases such as DIC or deep vein thrombosis. The FDP test uses latex particles coated with anti-D and anti-E. When mixed with plasma, these antibodies react with D and E fragments of both fibrin and fibrinogen, forming a clump.

The D-dimer test measures only the D fragments of fibrin that are covalently bound together. When a fibrin clot is stabilized by factor XIIIa, the D domains of adjacent molecules become linked together. The action of plasmin causes these to be released from the clot as a dimer, which is a molecule composed of two identical simpler molecules. Therefore, the D-dimer test will be positive only when fibrin degradation has occurred. This happens in DIC, after thromboembolytic therapy, and in such thrombotic conditions as deep vein thrombosis and pulmonary embolism, but does not occur in primary fibrinogenolysis.

D-dimer is detected by a latex agglutination test. Latex particles coated with anti-D that bind only to D-dimer are used. These particles will clump when mixed with serum that has an increased level of D-dimer. Since D-dimer levels parallel the amount of fibrinolytic activity in DIC, a quantitative test is often used to evaluate the severity of the disease. The test used is a two-site double antibody sandwich immunoassay.

PrecautionsBlood for FDP testing is collected by venipuncture into tubes containing EDTA, citrate, or heparin anticoagulant. The nurse or phlebotomist performing this procudure should follow universal precautions for the prevention of transmission of bloodborne pathogens. Performing a venipuncture to obtain a blood sample for the D-dimer test may be contraindicated if the patient is exhibiting prolonged bleeding from other sites. In this case the nurse or phlebotomist should consult the testing physician, who will determine an alternate means of obtaining a blood sample (such as placement of a catheter). There are no other notable precautions associated with performing the D-dimer test.

PreparationThere is no special preparation for the D-dimer test. No fasting is required.

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AftercareFollowing venipuncture to obtain blood samples for the D-dimer test, the laboratory technologist, nurse, or phlebotomist drawing the sample should apply pressure to the site to stop any residual bleeding. The venipuncture site should then be carefully inspected to make sure that the wound has closed and no bleeding is present. If bleeding continues even after pressure is applied, this event should be reported to the testing physician.

ComplicationsDIC often involves a rapidly changing hemostatic condition. Patients with DIC or thrombosis may be in serious condition and will likely not be ambulatory; more typically, patients with suspected DIC or thrombosis will be hospitalized. Nurses should be alert to any change in the patient's condition. Noticeable changes in the patient's condition at the time of venipuncture should be reported to the patient's physician. The venipuncture site should be examined for bleeding and any prolonged bleeding that cannot be stopped by applying pressure should be reported to the physician immediately.

KEY TERMS

D-dimer—A fibrin degradation fragment or product that is produced by the action of plasmin on fibrin in the clot dissolution process.

Disseminated intravascular coagulation (DIC)— A disruption in hemostasis in response to an underlying disease or trauma. It is associated with the release of a tissue factor that triggers coagulation and activates rapid thrombin formation and fibrinolysis throughout the vascular system.

Fibrin—A protein formed in the blood as an important component of the coagulation process.

Fibrin degradation products—Known also as fibrin split products, fibrin degradation products are formed when the fibrinolytic system is activated in response to the formation of clots in the vascular system. Fibrin degradation products, including D-dimer, will be present in fibrinolysis or thrombosis.

Fibrinolysis—The dissolution of clots by an activated fibrinolytic system. When clot formation occurs, the fibrinolytic system activates factors that lead to the formation of plasmin, which degenerates the fibrin in the clot.

Hemostasis—A regulating process that maintains blood in a fluid state and prevents the loss of blood through clot formation when the vascular system is compromised.

Plasmin—Plasmin is an enzyme formed in the activation of the fibrinolytic system to dissolve clots. Plasmin breaks down the fibrin in a clot into the fragments that are known as fibrin degradation products.

Thrombolytic drugs—Anticoagulants used to inhibit clotting. Thrombolytic therapy is used when increased fibrin degradation products are present, such as in patients who have had a heart attack or who have a compromised coagulation mechanism or a history of thrombosis.

Thrombosis—The presence of a clot or clots in the vascular system.

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ResultsReference ranges for FDP tests will vary according to the test method used and the laboratory performing the test. Qualitative results may be reported only as positive or negative. Typical FDP results are listed below.

Undiluted plasma is negative (no clumping): FDP is reported as less than 2 micrograms/mL.

A clumping reaction is reported as positive. If plasma is diluted, reporting is as follows: If the undiluted plasma only is positive: equal to or greater than 2 mcg/mL but less than 10 mcg/mL. If a 1:5 dilution of plasma is positive: equal to or greater than 10 mcg/mL but less then 80 mcg/mL. If a 1:20 dilution is positive: equal to or greater than 80 mcg/mL.

D-dimer results are reported as follows. Qualitative negative: less than 250 nanograms/mL. Qualitative positive: equal to or greater than 250 ng/mL. Quantitative: normally less than 250 ng/mL or less than 250 micrograms/L.

Health care team rolesA physician orders the FDP tests and interprets them. The testing physician must obtain an accurate patient history, especially to determine if the patient is taking any drugs that can affect the test results and to learn about any recent illness, trauma, or symptoms that could be related to DIC or thrombosis. The procedure should be explained to the patient by the unit nurse, who should be aware of the degree of seriousness of the patient's condition. FDP tests are performed by clinical laboratory scientists/medical technologists or by clinical laboratory technicians/medical laboratory technicians.

Training

Laboratory technologists performing D-dimer tests will have studied hematology and coagulation, enabling them to understand coagulation and the fibrinolytic system. Hands-on clinical laboratory training will prepare technologists to perform agglutination tests or monoclonal antibody tests for D-dimer. Nursing personnel responsible for patients undergoing D-dimer testing will understand the patient's condition and will be trained to observe changes that may signal a critical hemostatic event.

ResourcesBOOKSJacobs, David S. Laboratory Test Handbook, 5th ed. Hudson, OH: Lexi-Comp Inc., 2001.

Pagana, Kathleen D., and Timothy J. Pagana. Manual of Diagnostic and Laboratory Tests.St. Louis, MO: Mosby, Inc., 1998.

"Hemostasis and Coagulation Disorders." Sec. 11, Chapter 131, Merck Manual Online, 17th ed. Whitehouse Station, NJ: Merck & Co., Inc. 2001. <http://www.merck.com/pubs>.

ORGANIZATIONSAmerican Nurses Association. 600 Maryland Ave. SW, Ste. 100 West, Washington, DC 20024. (800)274-4ANA. <http://www.nursingworld.org>.

American Society of Clinical Pathologists. 2100 West Harrison St., Chicago, IL 60612 (312) 738-1336. <http://www.ascp.org>.

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Cite this page as follows:

"Fibrin Degradation Products Test." Encyclopedia of Nursing & Allied Health. Ed. Kristine Krapp. Gale Cengage, 2002. eNotes.com. 2006. 7 Oct, 2011 <http://www.enotes.com/nursing-encyclopedia/fibrin-degradation-products-test>

http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9290

Unit Code 9290:D-Dimer, Plasma

Useful For

Diagnosis of intravascular coagulation and fibrinolysis (ICF), also known as disseminated intravascular coagulation (DIC), especially when combined with clinical information and other laboratory test data (eg, platelet count, assays of

clottable fibrinogen and soluble fibrin monomer complex, and clotting time assays--prothrombin time and activated partial thromboplastin time).(2)

Excluding the diagnosis of acute pulmonary embolism (PE) or deep vein thrombosis (DVT), particularly when results of a sensitive D-dimer assay are combined with clinical information, including pretest disease probability.(3-6)

Clinical Information Thrombin, the terminal enzyme of the plasma procoagulant cascade, cleaves fibrinopeptides A and B from fibrinogen, generating fibrin monomer. Fibrin monomer contains D domains on each end of the molecule and a central E domain. Most of the fibrin monomers polymerize to form insoluble fibrin, or the fibrin clot, by repetitive end-to-end alignment of the D domains of 2 adjacent molecules in lateral contact with the E domain of a third molecule. The fibrin clot is subsequently stabilized by thrombin-activated factor XIII, which covalently cross-links fibrin monomers by transamidation, including dimerization of the D domains of adjacently polymerized fibrin monomers.

The fibrin clot promotes activation of fibrinolysis by catalyzing the activation of plasminogen (by plasminogen activators) to form plasmin enzyme. Plasmin proteolytically degrades cross-linked fibrin, ultimately producing soluble fibrin degradation products of various sizes that include cross-linked fragments containing neoantigenic D-dimer (DD) epitopes. Plasmin also degrades fibrinogen to form fragments X, Y, D, and E. D-dimer immunoassays use monoclonal antibodies to DD neoantigen and mainly detect cross-linked fibrin degradation products, whereas the fibrino(geno)lytic degradation products X, Y, D, and E and their polymers may be derived from fibrinogen or fibrin. Therefore, the blood content of D-dimer indirectly reflects the generation of thrombin and plasmin, roughly indicating the turnover or activation state of the coupled blood procoagulant and fibrinolytic mechanisms.

Reference Values < or =250 ng/mL D-Dimer Units (DDU)

< or =0.5 mcg/mL Fibrinogen Equivalent Units (FEU)

Interpretation

D-dimer values < or =250 ng/mL DDU (< or =0.50 mcg/mL FEU) are normal. Within the reportable normal range (110-250 ng/mL DDU; 0.22-0.50 mcg/mL FEU), measured values may reflect the activation state of the procoagulant and fibrinolytic systems, but the clinical utility of such quantitation is not established.

 

A normal D-dimer result (< or =250 ng/mL DDU; < or =0.50 g/mL FEU) has a negative predictive value of approximately 95% for the exclusion of acute pulmonary embolism (PE) or deep vein thrombosis when there is low or moderate pretest PE probability.

 

Increased D-dimer values are abnormal but do not indicate a specific disease state. D-dimer values may be increased as a result of:

-Clinical or subclinical disseminated intravascular coagulation/intravascular coagulation and fibrinolysis

-Other conditions associated with increased activation of the procoagulant and fibrinolytic mechanisms such as recent surgery, active or recent bleeding, hematomas, trauma, or thromboembolism

-Association with pregnancy, liver disease, inflammation, malignancy or hypercoagulable (procoagulant) states

The degree of D-dimer increase does not definitely correlate with the clinical severity of associated disease states.

Cautions

Lipemia can interfere with this assay, occasionally causing an under-estimation of the D-dimer level. Therefore, results from lipemic specimens should be interpreted with caution.

The presence of rheumatoid factor at a level >50 IU/mL may lead to an over-estimation of the D-dimer level.

Supportive Data

In Mayo studies examining sensitivity and specificity of D-dimer assays for excluding acute pulmonary embolism (PE) (diagnosed by pulmonary angiography), this automated latex immunoassay method compared well with manual enzyme-linked immunoassays and with a manual latex immunoassay. The negative predictive value of a normal D-dimer by automated latex assay result is approximately 95%, at the 300 ng/mL discriminant level, for excluding acute PE when combined with clinical information (see Interpretation). Clinical correlative evaluation of 98 patients studied for conditions other than acute PE suggests sensitivity approximately 95% and specificity approximately 95% for this method of D-dimer detection in various disease states.

http://www.muschealth.com/lab/content.aspx?id=150196

D-dimer assayWhat is this test?This test measures the amount of D-dimer in blood. This test is used to help evaluate conditions resulting from the formation of blood clots in blood vessels[1][2][3]. This test may be used when conditions such as acute deep vein thrombosis (DVT)[1][4][5] or disseminated intravascular coagulation (DIC) are suspected[6][7][8][9].What are related tests?

Disseminated intravascular coagulation screen Computed tomography venography CT angiography of pulmonary artery Ultrasonography for deep vein thrombosis

Why do I need this test?Laboratory tests may be done for many reasons. Tests are performed for routine health screenings or if a disease or toxicity is suspected. Lab tests may be used to determine if a medical condition is improving or worsening. Lab tests may also be used to measure the success or failure of a medication or treatment plan. Lab tests may be ordered for professional or legal reasons. The following are possible reasons why this test may be done:

Blood clot in the lung Cerebral venous sinus thrombosis Deep vein clot DIC - Disseminated intravascular coagulation Pre-eclampsia Splitting apart of aorta Systemic infection

When and how often should I have this test?When and how often laboratory tests are done may depend on many factors. The timing of laboratory tests may rely on the results or completion of other tests, procedures, or treatments. Lab tests may be performed immediately in an emergency, or tests may be delayed as a condition is treated or monitored. A test may be suggested or become necessary when certain signs or symptoms appear.

Due to changes in the way your body naturally functions through the course of a day, lab tests may need to be performed at a certain time of day. If you have prepared for a test by changing your food or fluid intake, lab tests may be timed in accordance with those changes. Timing of tests may be based on increased and decreased levels of medications, drugs or other substances in the body.

The age or gender of the person being tested may affect when and how often a lab test is required. Chronic or progressive conditions may need ongoing monitoring through the use of lab tests. Conditions that worsen and improve may also need frequent monitoring. Certain tests may be repeated to obtain a series of results, or tests may need to be repeated to confirm or disprove results. Timing and frequency of lab tests may vary if they are performed for professional or legal reasons.

How should I get ready for the test?Before having blood collected, tell the person drawing your blood if you are allergic to latex. Tell the healthcare worker if you have a medical condition or are using a medication or supplement that causes excessive bleeding. Also tell the healthcare worker if you have felt nauseated, lightheaded, or have fainted while having blood drawn in the past.

Tell the person doing the test if you are pregnant[2].

How is the test done?When a blood sample from a vein is needed, a vein in your arm is usually selected. A tourniquet (large rubber strap) may be secured above the vein. The skin over the vein will be cleaned, and a needle will be inserted. You will be asked to hold very still while your blood is collected. Blood will be collected into one or more tubes, and the tourniquet will be removed. When enough blood has been collected, the healthcare worker will take the needle out.How will the test feel?The amount of discomfort you feel will depend on many factors, including your sensitivity to pain. Communicate how you are feeling with the person doing the test. Inform the person doing the test if you feel that you cannot continue with the test.

During a blood draw, you may feel mild discomfort at the location where the blood sample is being collected.

What should I do after the test?After a blood sample is collected from your vein, a bandage, cotton ball, or gauze may be placed on the area where the needle was inserted. You may be asked to apply pressure to the area. Avoid strenuous exercise immediately after your blood draw. Contact your healthcare worker if you feel pain or see redness, swelling, or discharge from the puncture site.

What are the risks?Blood: During a blood draw, a hematoma (blood-filled bump under the skin) or slight bleeding from the puncture site may occur. After a blood draw, a bruise or infection may occur at the puncture site. The person doing this test may need to perform it more than once. Talk to your healthcare worker if you have any concerns about the risks of this test.

What are normal results for this test?Laboratory test results may vary depending on your age, gender, health history, the method used for the test, and many other factors. If your results are different from the results suggested below, this may not mean that you have a disease. Contact your healthcare worker if you have any questions. The following is considered to be a normal result for this test:

Adults:<0.5 mcg/mL (<0.5 mg/L) [10]

What might affect my test results? Results increased in:

o Trauma [11]o Cancer [11]o Infection [11]o Pregnancy [2]o Increased age [12]o Decreased renal function [13]

o Liver disease [13]o Burns [13]o Stroke/cerebrovascular disease [14][15]o Peripheral vascular disease [15]

What follow up should I do after this test?Ask your healthcare worker how you will be informed of the test results. You may be asked to call for results, schedule an appointment to discuss results, or notified of results by mail. Follow up care varies depending on many factors related to your test. Sometimes there is no follow up after you have been notified of test results. At other times follow up may be suggested or necessary. Some examples of follow up care include changes to medication or treatment plans, referral to a specialist, more or less frequent monitoring, and additional tests or procedures. Talk with your healthcare worker about any concerns or questions you have regarding follow up care or instructions. Where can I get more information?Related Companies

National Heart, Lung and Blood Institute

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D-dimer Blood Test - D Dimer Blood Testing, Reasons, Procedure to Conduct and Preparations for D Dimer Blood Test

D- Dimer Blood Testing

The D-dimers blood test is at test that is conducted to detect the possibility of deep vein thrombosis or even a pulmonary embolism. D-dimer is fibrin degradation product that roams in the blood waiting to be excreted and is a result of the breakdown of blood clots in the body by an enzyme like plasmin. Clots are extremely complex from a molecular perspective. They are formed by the action of thrombin and fibrogen that create a series of D-dimer matrices around the site of an injury and further clotting factors turn this matrix of clots into a cross-linked structure giving it immense strength and sealing power. When a clot is broken down by an enzyme like plasmin, the cross-linked structure and the matrices are broken, but the D-dimer of a blood clot cannot be broken down. This results in this molecule roaming in the blood stream until it is excreted.

Reasons for D-dimer Blood Test

The test is performed to check and confirm the presence of thrombosis in the body. More importantly, it can also indicate the imminence of a pulmonary embolism as well. An embolism is the movement of a solid fragment from one part of the body to another – in this case, a solid clot; as the amount of d-dimer increases in the blood the more likely an embolism. When an embolism reaches the lungs, it can be fatal, and is called a pulmonary embolism.

Procedure to Conduct D-dimer Blood Test

The D-dimer test is done by various methods including the ELISA assay. This test is conducted by simply taking a blood sample from the patient and then analyzing the blood for the presence of the protein in the blood. The evaluated D-dimer blood test reference ranges are 0-300 nanograms/milliliter. Any value above this measurement is considered dangerous. In many instances, the test is just secondary and most doctors will start treatment with drugs like heparin and warfarin for the thrombosis. Warfarin should ideally not be used on pregnant women because it is teratogenic, and will cause severe birth defects in the child.

Preparation for D-dimer Blood Test

There is no preparation that is required to be done for the test though you must inform the person taking the blood that you might be on blood thinners or anticoagulant medication and any diseases like liver disease and rheumatoid arthritis. There are some herbs that are also able to replicate the effects of blood thinning medication.

Submitted on December 9, 2009

http://labtestsonline.org/understanding/analytes/d-dimer/tab/test#how

D-dimer

Also known as: Fragment D-dimer; Fibrin degradation fragment

Formal name: D-dimer

Related tests: Fibrin Degradation Products (FDP); Fibrin Split Products (FSP); Prothrombin Time (PT); Partial Thromboplastin Time (PTT); Fibrinogen; Platelet Count

How is it used?

D-dimer tests are ordered, along with other laboratory tests and imaging scans, to help rule out the presence of a thrombus. Some of the conditions that the d-dimer test is used to help rule out include:

Deep vein thrombosis (DVT) Pulmonary embolism (PE) Strokes

This test may be used to determine if further testing is necessary to help diagnose diseases and conditions that cause hypercoagulability, a tendency to clot inappropriately.

A D-dimer level may be used to help diagnose disseminated intravascular coagulation (DIC) and to monitor the effectiveness of DIC treatment.

When is it ordered?

D-dimer may be ordered when someone has symptoms of DVT, such as:

Leg pain or tenderness, usually in one leg Leg swelling, edema Discoloration of the leg

It may be ordered when someone has symptoms of pulmonary embolism such as:

Sudden shortness of breath, labored breathing Coughing, hemoptysis (blood present in sputum) Lung-related chest pain Rapid heart rate

D-dimer is especially useful when the doctor thinks that something other than DVT or PE is causing the symptoms. It is a quick, non-invasive way for the doctor to help rule out abnormal or excess clotting.

When a person has symptoms of DIC, such as bleeding gums, nausea, vomiting, severe muscle and abdominal pain, seizures, and decreased urine output, a D-dimer test may be ordered, along with a PT, PTT, fibrinogen, and platelet count to help diagnose the condition. D-dimer may also be ordered at intervals when a patient is undergoing treatment for DIC to help monitor its progress.

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What does the test result mean?

A normal or negative D-dimer result means that it is most likely that the person tested does not have an acute condition or disease that is causing abnormal clot formation and breakdown. Most doctors agree that a negative D-dimer is most valid and useful when the test is done on people who are considered to be at low to intermediate risk for thrombosis. The test is used to help rule out clotting as the cause of symptoms.

A positive D-dimer result may indicate the presence of an abnormally high level of fibrin degradation products. It tells the doctor that there may be significant blood clot (thrombus) formation and breakdown in the body, but it does

not tell the location or cause. It may be due to, for example, a venous thromboembolism (VTE) or DIC. Typically, the D-dimer level is very elevated in DIC.

However, an elevated D-dimer does not always indicate the presence of a clot because a number of other factors can cause an increased level. Elevated levels may be seen in conditions in which fibrin is formed and then broken down, such as recent surgery, trauma, infection, heart disease, and some cancers or conditions in which fibrin is not cleared normally, such as liver disease. Therefore, D-dimer is typically not used to rule out VTE in hospitalized patients (inpatient setting).

Pregnancy is also a condition in which fibrin is formed and broken down and may result in an elevated D-dimer level. However, if DIC is suspected in a woman who is pregnant or is in the immediate postpartum period, then the D-dimer test may be used, along with a PT, PTT, fibrinogen, and platelet count to help diagnose her condition. If the woman has DIC, her D-dimer level will be very elevated.

D-dimer is recommended as an adjunct test. It should not be the only test used to diagnose a disease or condition. Both increased and normal D-dimer levels may require followup and can lead to further testing.

When used to monitor DIC treatment, decreasing levels indicate that treatment is effective while increasing levels may indicate that treatment is not working.

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Is there anything else I should know?

D-dimer concentrations may rise in the elderly, and false positives may be seen with high levels of rheumatoid factor, a protein seen in patients with rheumatoid arthritis. Substances such as high triglycerides, lipemia, and bilirubin can also cause false positives as can hemolysis caused by improper sample collection and handling.

There are several different methods of testing for D-dimer. Most of the D-dimer tests that yield quantitative results are done in a hospital lab, while those that yield qualitative or semi-quantitative results are performed at the patient's bedside (point of care).

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Immunoassay Tests

> Products

D-Dimer Plasmin Inhibitor Plasminogen

http://www.associatepublisher.com/e/d/d/d-dimer.htm#hd7

D-dimerD-dimer is a blood test performed in the medical laboratory to diagnose thrombosis. Since its introduction in the 1990s, it has become an important test performed in patients suspected of thrombotic disorders. While a negative result practically rules out thrombosis, a positive result can indicate thrombosis but also has other potential causes. Its main use, therefore, is to exclude thromboembolic disease where the probability is low.

IndicationsD-dimer testing is of clinical use when there is a suspicion of deep venous thrombosis (DVT) or pulmonary embolism (PE). In patients suspected of disseminated intravascular coagulation (DIC), D-dimers may aid in the diagnosis.

For DVT and PE, there are various scoring systems that are used to determine the a priori clinical probability of these diseases; the best-known were introduced by Wells et al (2003).* In a very high score, a D-dimer will make little difference, and anticoagulant therapy will be initiated regardless of test results.* In a moderate or low score:** A negative D-dimer test will virtually rule out thromboembolism.** If the D-dimer reads high, then further testing (ultrasound of the leg veins or lung scintigraphy or CT scanning) is required to confirm the presence of thrombus before anticoagulant therapy can be continued.

Reference rangeMost sampling kits have 0-300 ng/ml as normal range. Values exceeding 250, 300 or 500 ng/ml (different for various kits) are considered positive.

Types of assays* ELISA (e.g. SimpliRED®, Vidas®)* Latex turbidimetric assay (automated immunoassay, e.g. Roche Tina-quant®, MDA D-dimer®)* Enhanced microlatex* Latex-enhanced photometric

Principles

Principles of D-dimer testingFibrin degradation products (FDPs) are formed whenever fibrin is broken down by enzymes (e.g. plasmin). Determining FDPs is not considered useful, as this does not indicate whether the fibrin is part of a blood clot (or being generated as part of inflammation).

D-dimers are unique in that they are the breakdown products of a fibrin mesh that has been stabilised by Factor XIII. This factor crosslinks the E-element to two D-elements. This is the final step in the generation of a thrombus.

Plasmin is a natural fibrinolytic enzyme that organises clots and breaks down the fibrin mesh. It cannot, however, break down the bonds between one E and two D units. The protein fragment thus left over is a D-dimer.

D-dimer assays rely on monoclonal antibodies to bind to this specific protein fragment. The first patented MoAb of the kind was D Dimer-3B6/22, although others have been developed.

Sensitivity and specificityVarious kits have a 93-95% sensitivity and about 50% specificity in the diagnosis of thrombotic disease (Schrecengost et al 2003).* False positive readings can be due to various causes: liver disease, high rheumatoid factor, inflammation, malignancy, trauma, pregnancy, recent surgery as well as advanced age* False negative readings can occur if the sample is taken either too early after thrombus formation or if testing is delayed for several days. Additionally, the presence of anti-coagulation can render the test negative because it prevents thrombus extension.

HistoryD-dimer testing was originally developed in the diagnosis of disseminated intravascular coagulation. In the 1990s, they turned out to be useful in thromboembolic disorders.

References* Schrecengost JE, LeGallo RD, Boyd JC, Moons KG, Gonias SL, Rose CE Jr, Bruns DE. Comparison of diagnostic accuracies in outpatients and hospitalized patients of D-dimer testing for the evaluation of suspected pulmonary embolism. Clin Chem 2003;49:1483-90. PMID 12928229.* Wells PS, Anderson DR, Rodger M, Forgie M, Kearon C, Dreyer J, Kovacs G, Mitchell M, Lewandowski B, Kovacs MJ. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003;349:1227-35. PMID 14507948.

External link* D-dimer reference centre (site of a manufacturer of D-dimer sampling kits)

http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=9290

Unit Code 9290:D-Dimer, Plasma

Useful For

Diagnosis of intravascular coagulation and fibrinolysis (ICF), also known as disseminated intravascular coagulation (DIC), especially when combined with clinical information and other laboratory test data (eg, platelet count, assays of clottable fibrinogen and soluble fibrin monomer complex, and clotting time assays--prothrombin time and activated partial thromboplastin time).(2)

 

Excluding the diagnosis of acute pulmonary embolism (PE) or deep vein thrombosis (DVT), particularly when results of a sensitive D-dimer assay are combined with clinical information, including pretest disease probability.(3-6)

Method Name

Immunoassay TurbidimetricCoagulation testing is highly complex, oftenrequiring the performance of multiple assays andcorrelation with clinical information. For thatreason, we suggest ordering "CoagulationConsulatations."

Reporting Name

D-Dimer, P

Ordering Mnemonic

DDI

Aliases

Soft-DDI

Specimen Type

Plasma

Specimen Required

Container/Tube: Light blue-top (3.2% sodium citrate) tube(s)

Specimen Volume: 1 mL of platelet-poor plasma

Collection Instructions: Send specimen in plastic vial.

Specimen Minimum Volume

0.5 mL

Reject Due To

Specimens Other Than: Plasma

Anticoagulants Other Than: Sodium citrate

Hemolysis: Mild OK; gross reject

Thawing: Warm reject; Cold refreeze, send note to lab

Lipemia: Mild OK; gross reject

Transport Temperature

Frozen\Refrig NO\Ambient NO

Clinical Information

Thrombin, the terminal enzyme of the plasma procoagulant cascade, cleaves fibrinopeptides A and B from fibrinogen, generating fibrin monomer. Fibrin monomer contains D domains on each end of the molecule and a central E domain. Most of the fibrin monomers polymerize to form insoluble fibrin, or the fibrin clot, by repetitive end-to-end alignment of the D domains of 2 adjacent molecules in lateral contact with the E domain of a third molecule. The fibrin clot is subsequently stabilized by thrombin-activated factor XIII, which covalently cross-links fibrin monomers by transamidation, including dimerization of the D domains of adjacently polymerized fibrin monomers.

 

The fibrin clot promotes activation of fibrinolysis by catalyzing the activation of plasminogen (by plasminogen activators) to form plasmin enzyme. Plasmin proteolytically degrades cross-linked fibrin, ultimately producing soluble fibrin degradation products of various sizes that include cross-linked fragments containing neoantigenic D-

dimer (DD) epitopes. Plasmin also degrades fibrinogen to form fragments X, Y, D, and E. D-dimer immunoassays use monoclonal antibodies to DD neoantigen and mainly detect cross-linked fibrin degradation products, whereas the fibrino(geno)lytic degradation products X, Y, D, and E and their polymers may be derived from fibrinogen or fibrin. Therefore, the blood content of D-dimer indirectly reflects the generation of thrombin and plasmin, roughly indicating the turnover or activation state of the coupled blood procoagulant and fibrinolytic mechanisms.

Reference Values

< or =250 ng/mL D-Dimer Units (DDU)

< or =0.5 mcg/mL Fibrinogen Equivalent Units (FEU)

Interpretation

D-dimer values < or =250 ng/mL DDU (< or =0.50 mcg/mL FEU) are normal. Within the reportable normal range (110-250 ng/mL DDU; 0.22-0.50 mcg/mL FEU), measured values may reflect the activation state of the procoagulant and fibrinolytic systems, but the clinical utility of such quantitation is not established.

 

A normal D-dimer result (< or =250 ng/mL DDU; < or =0.50 g/mL FEU) has a negative predictive value of approximately 95% for the exclusion of acute pulmonary embolism (PE) or deep vein thrombosis when there is low or moderate pretest PE probability.

 

Increased D-dimer values are abnormal but do not indicate a specific disease state. D-dimer values may be increased as a result of:

-Clinical or subclinical disseminated intravascular coagulation/intravascular coagulation and fibrinolysis

-Other conditions associated with increased activation of the procoagulant and fibrinolytic mechanisms such as recent surgery, active or recent bleeding, hematomas, trauma, or thromboembolism

-Association with pregnancy, liver disease, inflammation, malignancy or hypercoagulable (procoagulant) states

The degree of D-dimer increase does not definitely correlate with the clinical severity of associated disease states.

Cautions

Lipemia can interfere with this assay, occasionally causing an under-estimation of the D-dimer level. Therefore, results from lipemic specimens should be interpreted with caution.

 

The presence of rheumatoid factor at a level >50 IU/mL may lead to an over-estimation of the D-dimer level.

Supportive Data

In Mayo studies examining sensitivity and specificity of D-dimer assays for excluding acute pulmonary embolism (PE) (diagnosed by pulmonary angiography), this automated latex immunoassay method compared well with manual enzyme-linked immunoassays and with a manual latex immunoassay. The negative predictive value of a normal D-dimer by automated latex assay result is approximately 95%, at the 300 ng/mL discriminant level, for excluding acute PE when combined with clinical information (see Interpretation). Clinical correlative evaluation of 98 patients studied for conditions other than acute PE suggests sensitivity approximately 95% and specificity approximately 95% for this method of D-dimer detection in various disease states.

Method Description

The principle of the test is as follows. When a beam of monochromatic light is allowed to transverse a suspension of microlatex particles to which specific antibodies have been attached by covalent bonding and if the wavelength of the light is much greater than the diameter of the latex particles, the light is only slightly absorbed. In the presenceof the antigen being tested for, the antibody-coated latex particles agglutinate to form aggregates of a diameter greater than the wavelength of the light, more of the latter is absorbed. This increase in light absorption is a function of the antigen level present in the test sample. (Package insert: STA-LIATEST D-DI, Diagnostica Stago, Inc.)

Day(s) and Time(s) Test Performed Monday through Sunday; Continuously

Analytic Time 1 day

Maximum Laboratory Time 1 day

Specimen Retention Time 8 hours

Performing Laboratory Location Rochester

Test Classification This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions.

CPT Code Information 85379

http://www.d-dimer.co.uk/simpliRED.asp?navid=3

D-dimer Explained

During blood coagulation, fibrinogen is converted to fibrin by the activation of thrombin. Fibrin monomers polymerise to form a soluble gel of non-cross linked fibrin. The fibrin gel is then converted to cross linked fibrin by thrombin activated factor XIII to form an insoluble clot. To prevent complete obstruction of circulation, clot lysis is triggered by plasmin at the same time as a clot forms. This is called fibrinolysis. Fibrinogen, fibrin and cross linked fibrin are all cleaved by plasmin during fibrinolysis but only degradation products from cross linked fibrin contain D-dimer. Therefore, D-dimer is a marker of active coagulation and fibrinolysis.

 

The link between raised D-dimer levels and thrombotic conditions such as deep vein thrombosis (DVT) and pulmonary embolism (PE) is well established. D-dimer testing is used as an aid in the diagnosis of both of these conditions (often collectively referred to as venous thrombembolism or VTE) as well as disseminated intravascular coagulation and hence plays an important role in the effective management of these serious clinical conditions.

  SimpliRED D-dimer Principle SimpliRED D-dimer is a whole blood agglutination assay for the identification of D-dimer. The active component is a conjugate of D-dimer specific monoclonal antibody joined to a monoclonal antibody that binds to the outside of red blood cells. When this bi-specific conjugate is mixed with patient whole blood, agglutination of the red blood cells will occur if the D-dimer concentration is above the cut-off level. In the absence of D-dimer, no agglutination takes place. The crosslinked fibrin breakdown products D-dimer, D-dimer E and derivates with a high molecular weight are all recognised by SimpliRED D-dimer.